Pregnenolone to Reduce Stress-Induced Cocaine Craving and Improve Treatment Outcome

To test the preliminary efficacy of 200 mg and 400 mg of pregnenolone daily versus placebo in a dose-ranging study in individuals with cocaine use disorder. This proposal is a laboratory and treatment outcome study to examine the effects of pregnenolone on cocaine craving, mood and neurobiological reactivity to brief exposure to stress, drug cues and neutral situations in a sample of individuals with cocaine use disorder. We hypothesize that pregnenolone will be beneficial for reduction in stress and drug cue induced craving and related arousal. In a sample of 80 men and women with cocaine use disorder, we propose to examine (a) differences in measures of cocaine craving, emotion state, hypothalamic-pituitary-adrenal (HPA) activation, physiological arousal and plasma catecholamine response to stress imagery and to drug cue imagery as compared to neutral imagery; (b) reduction in cocaine abstinence symptoms; and (c) improvement in cocaine treatment outcomes as measured by increasing abstinence, reduction in cocaine use and increased treatment attendance and (d) sex differences in all of these outcomes.